Increased hepatic iron concentration in nonalcoholic steatohepatitis is associated with increased fibrosis
Increased hepatic iron concentration in nonalcoholic steatohepatitis is associated with increased fibrosis
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DOI：
10.1016/s0016-5085(98)70482-2
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发表时间：
1998-02-01
期刊：
影响因子：
29.4
通讯作者：
Powell, LW
中科院分区：
文献类型：
--
作者：
George, DK;Goldwurm, S;Powell, LW
背景和目的：非酒精性脂肪性肝炎（NASH）是一种慢性肝病，偶尔会进展为肝硬化，但通常呈良性病程。本研究的目的是探讨血色素沉着病突变 Cys282Tyr 在某些 NASH 患者出现的轻度肝铁超载中的作用及其与这些患者肝损伤的关系。方法：对 51 名 NASH 患者进行了研究。对所有患者检测了 Cys282Tyr 突变的存在，并对脂肪变性的组织学分级、炎症、Perls 染色、肝铁浓度 (HIC) 和血清铁指数进行了分析。结果：31% 的 NASH 患者为 Cys282Tyr 突变纯合子或杂合子。该突变与 Perls 染色等级 (P < 0.005)、HIC (P < 0.005) 和转铁蛋白饱和百分比 (P < 0.005) 显着相关，但与血清铁蛋白水平无关。线性回归分析显示，肝铁含量增加（Perls染色或HIC）与纤维化严重程度的相关性最大（P < 0.0001）。结论：Cys282Tyr 突变是导致 NASH 中发现的大部分轻度铁超负荷的原因，因此与这些患者的肝损伤具有显着相关性。因此，血色素沉着病基因突变的杂合性并不总是被认为是良性的。
Background & Aims: Nonalcoholic steatohepatitis (NASH) is a chronic liver disease that occasionally progresses to cirrhosis but usually has a benign course. The aim of this study was to investigate the role of the hemochromatosis mutation Cys282Tyr in development of the mild hepatic iron overload found in some patients with NASH and its association with hepatic damage in these patients. Methods: Fifty-one patients with NASH were studied. The presence of the Cys282Tyr mutation was tested in all patients, and the data were analyzed with respect to the histological grade of steatosis, inflammation, Perls' staining, hepatic iron concentration (HIC), and serum iron indices. Results: Thirty-one percent of patients with NASH were either homozygous or heterozygous for the Cys282Tyr mutation. This mutation was significantly associated with Perls' stain grade (P < 0.005), HIC (P < 0.005), and transferrin saturation percentage (P < 0.005) but not with serum ferritin levels. Linear regression analysis showed that increased hepatic iron (Perls' stain or HIC) had the greatest association with the severity of fibrosis (P < 0.0001). Conclusions: The Cys282Tyr mutation is responsible for most of the mild iron overload found in NASH and thus has a significant association with hepatic damage in these patients. Heterozygosity for the hemochromatosis gene mutation therefore cannot always be considered benign.